MCID: LKD010
MIFTS: 43

Leukodystrophy, Hypomyelinating, 2

Categories: Genetic diseases, Eye diseases, Fetal diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 2

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 2:

Name: Leukodystrophy, Hypomyelinating, 2 53 71 28 13 69
Pmld1 53 12 23 55 71
Hld2 53 12 23 71
Hypomyelinating Leukodystrophy 2 12 23 14
Pelizaeus-Merzbacher-Like Disease Due to Gjc2 Mutation 12 55
Pelizaeus-Merzbacher-Like Disease 1 12 23
Pelizaeus-Merzbacher-Like Disease Autosomal Recessive Type 1 71
Pelizaeus-Merzbacher-Like Disease, 1; Pmld1 53
Pelizaeus-Merzbacher-Like Disease Type 1 71
Pelizaeus-Merzbacher-Like Disease, 1 53
Pmldar1 71

Characteristics:

Orphanet epidemiological data:

55
pelizaeus-merzbacher-like disease due to gjc2 mutation
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
most children become wheelchair-bound
similar disorder to x-linked pelizaeus-merzbacher disease (pmd, )


HPO:

31
leukodystrophy, hypomyelinating, 2:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


Summaries for Leukodystrophy, Hypomyelinating, 2

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity that has material basis in homozygous or compound heterozygous mutation in the GJC2 gene on chromosome 1q42.

MalaCards based summary : Leukodystrophy, Hypomyelinating, 2, also known as pmld1, is related to pelizaeus-merzbacher-like disease and pelizaeus-merzbacher disease, and has symptoms including ataxia, seizures and dystonia. An important gene associated with Leukodystrophy, Hypomyelinating, 2 is GJC2 (Gap Junction Protein Gamma 2), and among its related pathways/superpathways are Neural Crest Differentiation and Glial Cell Differentiation. Related phenotypes are behavior/neurological and cellular

UniProtKB/Swiss-Prot : 71 Leukodystrophy, hypomyelinating, 2: An autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity.

Description from OMIM: 608804
GeneReviews: NBK470716

Related Diseases for Leukodystrophy, Hypomyelinating, 2

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 3 Leukodystrophy, Hypomyelinating, 2
Leukodystrophy, Hypomyelinating, 5 Leukodystrophy, Hypomyelinating, 4
Leukodystrophy, Hypomyelinating, 6 Leukodystrophy, Hypomyelinating, 9
Leukodystrophy, Hypomyelinating, 10 Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 12 Leukodystrophy, Hypomyelinating, 13

Diseases related to Leukodystrophy, Hypomyelinating, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 pelizaeus-merzbacher-like disease 30.8 GJB1 GJC2 PLP1 SNAP29
2 pelizaeus-merzbacher disease 30.5 GJC2 MBP PLP1
3 charcot-marie-tooth disease, x-linked dominant, 1 10.5 GJB1 GJC2
4 leukodystrophy, hypomyelinating, 4 10.4 GJC2 PLP1
5 hypomyelinating leukoencephalopathy 10.4 GJC2 PLP1
6 spastic paraplegia 2, x-linked 10.4 GJC2 PLP1
7 neurodegeneration with brain iron accumulation 2b 10.4 FA2H PANK2
8 hypomyelinating leukodystrophy 10.3 GJB1 GJC2 PLP1
9 allergic encephalomyelitis 10.3 MBP PLP1
10 cerebral degeneration 10.3 FA2H GJC2 PLP1
11 hallermann-streiff syndrome 10.2 GJB1 GJC2
12 leukodystrophy 10.2 FA2H GJC2 PLP1
13 neurodegeneration with brain iron accumulation 3 10.2 FA2H JPH3 PANK2
14 niemann-pick disease, type a 10.2 MBP PLP1
15 oromandibular dystonia 10.2 GCH1 TOR1A
16 neurodegeneration with brain iron accumulation 6 10.2 PANK2 VPS13A
17 segmental dystonia 10.2 GCH1 TOR1A
18 early-onset generalized dystonia 10.2 GCH1 TOR1A
19 extratemporal epilepsy 10.2 PLP1 TOR1A
20 neurodegeneration with brain iron accumulation 10.2 FA2H PANK2 VPS13A
21 focal hand dystonia 10.1 PANK2 TOR1A
22 choreoacanthocytosis 10.1 HCCS JPH3 VPS13A
23 blepharospasm 10.1 GCH1 TOR1A
24 hereditary spastic paraplegia 10.1 FA2H GJC2 PLP1
25 hereditary neuropathies 10.1 GJB1 MBP PLP1
26 thiamine metabolism dysfunction syndrome 2 10.1 GCH1 TOR1A
27 cranio-facial dystonia 10.1 GCH1 GJC2 TOR1A
28 cervical dystonia 10.1 GCH1 TOR1A
29 lymphedema, hereditary, ii 10.1 GCH1 GJC2 TOR1A
30 huntington disease-like 2 10.1 HTT JPH3
31 dystonia 1, torsion, autosomal dominant 10.0 GCH1 TOR1A
32 neurodegeneration with brain iron accumulation 1 10.0 FA2H JPH3 PANK2 VPS13A
33 hemidystonia 10.0 GCH1 TOR1A
34 dystonia 12 10.0 GCH1 PANK2 TOR1A
35 choreatic disease 9.9 HTT JPH3 VPS13A
36 neurodegeneration with brain iron accumulation 2a 9.9 FA2H PANK2
37 dystonia, dopa-responsive 9.8 GCH1 TOR1A
38 dystonia 9.7 FA2H GCH1 PANK2 TOR1A
39 central nervous system disease 9.6 HTT MBP PLP1
40 movement disease 9.4 GCH1 HTT PANK2 TOR1A

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 2:



Diseases related to Leukodystrophy, Hypomyelinating, 2

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 2

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
seizures
dystonia
head titubation
dysarthria
more
Head And Neck Eyes:
optic atrophy
myopia
rotary nystagmus

Head And Neck Face:
facial weakness

Head And Neck Head:
head titubation

Neurologic Peripheral Nervous System:
axonal sensory neuropathy
decreased motor nerve conduction velocities (ncv)
peripheral neuropathy, mild (less common)
demyelinating motor neuropathy


Clinical features from OMIM:

608804

Human phenotypes related to Leukodystrophy, Hypomyelinating, 2:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 seizures 31 HP:0001250
3 dystonia 31 HP:0001332
4 head titubation 31 HP:0002599
5 dysarthria 31 HP:0001260
6 facial palsy 31 HP:0010628
7 global developmental delay 31 HP:0001263
8 optic atrophy 31 HP:0000648
9 cognitive impairment 31 HP:0100543
10 myopia 31 HP:0000545
11 babinski sign 31 HP:0003487
12 intention tremor 31 HP:0002080
13 sensory axonal neuropathy 31 HP:0003390
14 decreased motor nerve conduction velocity 31 HP:0003431
15 rigidity 31 HP:0002063
16 progressive spasticity 31 HP:0002191
17 motor delay 31 HP:0001270
18 choreoathetosis 31 HP:0001266
19 cerebral atrophy 31 HP:0002059
20 leukodystrophy 31 HP:0002415
21 spastic paraparesis 31 HP:0002313
22 poor speech 31 HP:0002465
23 muscular hypotonia of the trunk 31 HP:0008936
24 cerebral hypomyelination 31 HP:0006808
25 rotary nystagmus 31 HP:0001583
26 demyelinating motor neuropathy 31 HP:0007220

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 2:


head titubation, facial paresis, action tremor, paraparesis, spastic, seizures, muscle rigidity, ataxia

MGI Mouse Phenotypes related to Leukodystrophy, Hypomyelinating, 2:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.29 DLL1 FA2H GJB1 GJC2 HTT JPH3
2 cellular MP:0005384 10.2 DLL1 GJB1 GJC2 HCCS HTT MBP
3 growth/size/body region MP:0005378 10.17 DLL1 GJB1 HCCS HTT JPH3 MBP
4 homeostasis/metabolism MP:0005376 10.15 NRAS PANK2 PLP1 SNAP29 TOR1A HCCS
5 mortality/aging MP:0010768 10.07 DLL1 GCH1 GJB1 GJC2 HCCS HTT
6 hematopoietic system MP:0005397 10.06 DLL1 GJB1 GJC2 HTT MBP NRAS
7 immune system MP:0005387 9.97 MBP NRAS PANK2 PLP1 VPS13A DLL1
8 nervous system MP:0003631 9.93 DLL1 FA2H GCH1 GJB1 GJC2 HTT
9 normal MP:0002873 9.5 DLL1 GJC2 HCCS HTT MBP NRAS
10 vision/eye MP:0005391 9.23 NRAS PANK2 PLP1 TOR1A FA2H GJB1

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 2

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 2

Genetic Tests for Leukodystrophy, Hypomyelinating, 2

Genetic tests related to Leukodystrophy, Hypomyelinating, 2:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 2 28 GJC2

Anatomical Context for Leukodystrophy, Hypomyelinating, 2

Publications for Leukodystrophy, Hypomyelinating, 2

Articles related to Leukodystrophy, Hypomyelinating, 2:

# Title Authors Year
1
Pelizaeus-Merzbacher disease, Pelizaeus-Merzbacher-like disease 1, and related hypomyelinating disorders. ( 22422208 )
2012
2
Pelizaeus-Merzbacher-Like Disease 1 ( 29276893 )
1993

Variations for Leukodystrophy, Hypomyelinating, 2

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

71
# Symbol AA change Variation ID SNP ID
1 GJC2 p.Pro90Ser VAR_023754 rs74315312
2 GJC2 p.Tyr272Asp VAR_023755 rs74315314
3 GJC2 p.Met286Thr VAR_023756 rs74315311

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

6 (show all 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 GJC2 NM_020435.3(GJC2): c.-167A> G single nucleotide variant Pathogenic rs587776888 GRCh37 Chromosome 1, 228337561: 228337561
2 GJC2 NM_020435.3(GJC2): c.787G> A (p.Glu263Lys) single nucleotide variant Pathogenic rs397514734 GRCh37 Chromosome 1, 228346246: 228346246
3 GJC2 NM_020435.3(GJC2): c.-170A> G single nucleotide variant Pathogenic rs587777496 GRCh37 Chromosome 1, 228337558: 228337558
4 GJC2 NM_020435.3(GJC2): c.857T> C (p.Met286Thr) single nucleotide variant Pathogenic rs74315311 GRCh37 Chromosome 1, 228346316: 228346316
5 GJC2 NM_020435.3(GJC2): c.268C> T (p.Pro90Ser) single nucleotide variant Pathogenic rs74315312 GRCh37 Chromosome 1, 228345727: 228345727
6 GJC2 NM_020435.3(GJC2): c.989delC (p.Pro330Argfs) deletion Pathogenic rs796065027 GRCh38 Chromosome 1, 228158747: 228158747
7 GJC2 NM_020435.3(GJC2): c.718C> T (p.Arg240Ter) single nucleotide variant Pathogenic rs74315313 GRCh37 Chromosome 1, 228346177: 228346177
8 GJC2 NM_020435.3(GJC2): c.814T> G (p.Tyr272Asp) single nucleotide variant Pathogenic rs74315314 GRCh37 Chromosome 1, 228346273: 228346273
9 GJC2 NM_020435.3(GJC2): c.914_947del34 (p.Pro305Argfs) deletion Pathogenic rs796065028 GRCh38 Chromosome 1, 228158672: 228158705
10 GJC2 NM_020435.3(GJC2): c.695_696insG (p.Tyr232Terfs) insertion Pathogenic rs796065029 GRCh38 Chromosome 1, 228158453: 228158454
11 GJC2 NM_020435.3(GJC2): c.78delG (p.Trp27Glyfs) deletion Likely pathogenic rs886039904 GRCh37 Chromosome 1, 228345537: 228345537
12 SNAP29 NM_004782.3(SNAP29): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs886041240 GRCh37 Chromosome 22, 21213400: 21213400
13 SNAP29 NM_004782.3(SNAP29): c.354dupG (p.Leu119Alafs) duplication Pathogenic rs886041263 GRCh37 Chromosome 22, 21224741: 21224741
14 GJC2 NM_020435.3(GJC2): c.1175C> G (p.Ser392Cys) single nucleotide variant Likely pathogenic GRCh37 Chromosome 1, 228346634: 228346634

Expression for Leukodystrophy, Hypomyelinating, 2

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 2.

Pathways for Leukodystrophy, Hypomyelinating, 2

Pathways related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.14 DLL1 GJB1 MBP
2 9.53 MBP PLP1

GO Terms for Leukodystrophy, Hypomyelinating, 2

Cellular components related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gap junction GO:0005921 9.16 GJB1 GJC2
2 myelin sheath GO:0043209 9.13 GJC2 MBP PLP1
3 connexin complex GO:0005922 8.62 GJB1 GJC2

Biological processes related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 astrocyte development GO:0014002 9.16 DLL1 PLP1
2 axon ensheathment GO:0008366 8.96 MBP PLP1
3 cell communication GO:0007154 8.8 DLL1 GJB1 GJC2

Molecular functions related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gap junction channel activity GO:0005243 8.96 GJB1 GJC2
2 structural constituent of myelin sheath GO:0019911 8.62 MBP PLP1

Sources for Leukodystrophy, Hypomyelinating, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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